One of the most unusual features of the disease that could hold the crucial key to a cure is that it manifests in women at about four times the rate it does in men.

It’s a mystery that has plagued researchers—until now. A recent studypublished in The Proceedings of the National Academy of Sciences highlights a mechanism in female biology that finally accounts for women experiencing higher rates of MS. The secret? Testosterone.

MS is an autoimmune disease, where immune cells enter the brain and spinal cord and mount an attack on the myelin sheath, the outer membrane that insulates the nerves and helps facilitates proper nerve signal conduction throughout the body. As a result, MS patients suffer from sensory disturbances, problems in cognition, and loss of proper motor control. Scientists have known for some time that females are more susceptible than men to developing MS (and autoimmune disorders in general), but testosterone’s role is only recently becoming apparent.

The finding could help illuminate current treatments, which aim to suppress the immune system right now. Certainly, that provides relief—but it also raises the potential for being unable to fight off infections.

Melissa Brown, an MS researcher at Northwestern University’s Feinberg School of Medicine and a coauthor of the new PNAS study, has been trying to uncover the source of MS’s mysterious gender difference. The breakthrough in the team’s latest findings are actually thanks to a mistake made by a new student in Brown’s lab several years ago. The lab almost exclusively used female mice for its investigations, studying mutations that would prevent MS progression. But when one of Brown’s newest students was tasked with collecting the mice for one of the investigations, she couldn’t correctly discern which were males and which were females—a common mistake for younger students.

The student accidentally pulled up a cohort of male mice, and brought them up for experimentation. “When she got her results, they were completely opposite from what we had seen in females,” says Brown. “The mutation’s protection—in both females and males—makes things much worse.”

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